The present invention relates to 14.alpha.-hydroxy-4-androstene-3,6,17-trione hydrate crystals and a process for producing the same.
14.alpha.-hydroxy-4-androstene-3,6,17-trione has a biological activity of human placenta-originating estrodiene synthesis enzyme inhibiting action and development thereof as an anticancer medicine has been expected.
14.alpha.-hydroxy-4-androstene-3,6,17-trione is a known compound and can be synthesized, for example, by the process disclosed in Japanese Patent Kokoku No. 1-32236 (EP-A 300062). According to this process, 6.beta.,14.alpha.-dihydroxy-4-androstene-3,17-dione is dissolved in chloroform and an oxidizing agent is added to the solution to carry out the reaction. After completion of the reaction, the reaction mixture is filtrated to remove the oxidizing agent and the residue is sufficiently washed. Then, the solvent is removed to obtain a crude fraction. This fraction is dissolved in a small amount of chloroform or methanol and the solution is subjected to high performance liquid chromatography (HPLC) to elute and isolate 14.alpha.-hydroxy-4-androstene-3,6,17-trione.
The 14.alpha.-hydroxy-4-androstene-3,6,17-trione is obtained as a crystal by distilling off the solvent from the organic solvent solution. The above patent publication mentions that thus obtained crystal is white, but strictly speaking this is yellow.
The 14.alpha.-hydroxy-4-androstene-3,6,17-trione which is first obtained in the form of an organic solvent solution and finally obtained by distilling off the solvent from the organic solvent solution is an anhydride crystal which has hygroscopicity and which changes its color upon absorption of water. Therefore, the compound is difficult to handle in the formulation step and is not suitable as preparations for medicines.
That is, the 14.alpha.-hydroxy-4-androstene-3,6,17-trione anhydride crystal (hereinafter referred to as ".alpha.-type crystal") readily absorbs water during storage or formulation and increases in its weight and changes to slightly yellowish white in its color. Therefore, when the .alpha.-type crystal is used, there occur errors in weighing, unevenness in the color of medicines prepared therefrom and differences in the color of respective lots of preparations. Thus, it is difficult to obtain medicines of uniform quality. Accordingly, the object of the present invention is to provide 14.alpha.-hydroxy-4-androstene-3,6,17-trione suitable as starting preparations for medicines.